In the art, sedimentation separators are known in order to achieve high viable cell concentrations in suspensions and to remove sensitive products, like highly glycosylated polypeptides and proteins. In one process, sedimentation settlers are used that are inclined from the vertical and comprise a plurality of long and narrow tubes or channels. Larger cells are removed from the suspension by settling onto the upward-facing surfaces of the settler, where they form thin sediment layers that slide down and are collected at the bottom of a vessel located underneath the sedimentation settler. An example of such sedimentation separator is shown in WO 03/020919.
With such sedimentation separator it is always desired to reduce the retention time of the cells in the separation apparatus in order to minimize the time cells and product is maintained under non-controlled conditions, e.g. outside the well controlled bioreactor in an external loop, thus to minimize cell and product damages to the cells. From this perspective, there is a need to have a collection vessel as small as possible. On the other hand, a high throughput is desired, which can be obtained by increasing the inflow volume or flow-through. This, on the other hand is disadvantageous as it may come along with undesirable turbulences of the flow within the collection vessel and can lead to increased dwell times by negative effects on the sedimentation behavior of the cells also negatively affecting process performances.
The potential of cell retention techniques for large-scale high-density perfusion culture of suspended mammalian cells is reported by Voisard, D., et al. (Biotechnol. Bioeng. 82 (2003) 751-765). Chary, S., reported in 2010 the achieving higher titers and higher run-rates through cell culture perfusion operations in the inoculum train (BioProduction Conference, 2010, Barcelona, Spain).
DE-A-36 19 926 describes an apparatus for treating a liquid containing a depositing contamination of solid particles, which apparatus includes at least one chamber through which the liquid can flow and which has liquid feed and outlet connections and which apparatus is furnished with guide surfaces to guide the liquid into the separation chamber. FIG. 2 of DE-A-36 19 926 shows a stationary separator being primarily designed to remove solid particles from water and oil. The separator includes a housing which houses a deposition chamber. The contaminated water is passed through the contaminated water supply and comes in a pre-separation chamber. Throughout the deposition, a low flow rate is adjusted so that the separation of the components occurs by the force of gravity. A portion of the oil collects in the pre-separation chamber already above and can be discharged through the oil drain. A portion of the solids sink to the bottom of the pre-separation chamber and comes down into the deposition chamber. The pre-treated water then flows with low flow rate through a package of dividers upwards.
EP-A-0 003 146 discloses a device for separating water and water-insoluble, light substances contained therein, for example, oil. The device comprises a reservoir for receiving a mixture of water and substances and a plurality of sequential, parallel, sloping separation channels arranged in the reservoir and bounded by channel walls, an inlet chamber, a mixture inlet opening out in the inlet chamber and distributing the mixture at right angles to the plane of the drawing, a feeding chamber communicating with the inlet chamber, a substance outlet, a layer-limit sensor, an overflow with an overflow rim, a water outlet communicating with the overflow and a screen separating the overflow from a collecting space for light substances. The assembly of separation channels is arranged between the feeding chamber and an outlet chamber of the reservoir. The mixture flows through a dosing member, in which flocculation promoting chemicals are added to the mixture and through a mixer towards the mixture inlet. The desired flocculation takes place in the feeding chamber.
Thus, in DE-A-36 19 926 and EP-A-0 003 146 the flow direction of the mixture is parallel to the separation plates, from the upper end of the separation plates towards the lower end of the separation plates, before the mixture enters the separation plates.